Carvedilol as an Adjunct to Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding

Carvedilol as an Adjunct to Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding

Carvedilol Plus Endoscopic Cyanoacrylate Injection Versus Endoscopic Cyanoacrylate Injection for Secondary Prophylaxis of Gastric Variceal Bleeding

Gastric variceal obturation is the current endoscopic therapy of choice for gastric variceal bleeding but is associated with a high rebleeding rate. Carvedilol is a potent non-selective β-blocker. The role of carvedilol in the prevention of recurrent gastric variceal bleeding is not studied. This study aimed at evaluating the efficacy of carvedilol as an adjunct to gastric variceal obturation in the secondary prophylaxis of gastric variceal bleeding.

Gastric variceal bleeding is a lethal complication of portal hypertension. The rebleeding rate ranged between 30% to 50% in patients after initial hemostasis. Endoscopic cyanoacrylate injection is currently the choice of endoscopic therapy of acute gastric variceal bleeding and prevention of recurrent bleeding. However, the rebleeding rate is still high in the patients undergoing repeated endoscopic cyanoacrylate injection. Non-selective β-blockers are frequently used for the secondary prophylaxis of variceal bleeding. In the case of esophageal varices, combination of non-selective β-blockers and endoscopic therapy significantly lowers the rebleeding rate compared with endoscopic therapy alone. However, propranolol failed to decrease the rebleeding rate as an adjunct to endoscopic cyanoacrylate injection and was associated with a higher incidence of adverse effects in gastric variceal bleeding patients. A more potent non-selective β-blocker than propranolol might further decrease portal pressure and decrease the rebleeding rate. Carvedilol is a potent non-selective β-blocker with both beta and alpha-1 blocker effect. It significantly lowers portal pressure even in propranolol non-responders. However, it is unclear weather carvedilol will play a role in the prevention of recurrent gastric variceal bleeding. The investigators conducted a randomized controlled trial to compare the efficacy of carvedilol combined with endoscopic cyanoacrylate injection with endoscopic cyanoacrylate injection alone in secondary prophylaxis of gastric variceal bleeding.

The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices. Oral carvedilol is administrated during the whole study period, starting at 6.25 mg daily and increased until the maximum tolerated dose.

The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.

Oral carvedilol is started after randomization at an initial dose of 6.25 mg daily. Doses are increased every 3 days during the admission or every 7 days in the out-patient clinics until the maximum tolerated dose was achieved or up to 25 mg daily, aiming at reducing resting pulse rate by 25 percent but not below 55 beats per minute with systolic blood pressure >90 mm Hg.

The patients undergo repeated endoscopic cyanoacrylate injection every 3-4 weeks until obturation of gastric varices.

Inclusion Criteria: Age of 20 to 80 years Cirrhotic patients with acute gastric variceal bleeding proven by an endoscopy within 24 h of bleeding Stable hemodynamic condition for at least 3 days after cyanoacrylate injection Exclusion Criteria: Previous treatment of gastric varices, including endoscopic therapy, transjugular intrahepatic porto-systemic shunt, or surgery Contraindications to non-selective beta-blockers or cyanoacrylate injection Serum total bilirubin >10 mg/dL Grade III/IV hepatic encephalopathy Hepato-renal syndrome Severe heart failure (NYHA Fc III/IV) Chronic kidney disease under renal replacement therapy Refractory ascites Malignancy other than hepatocellular carcinoma Pregnancy Pacemaker use Refusal to participate

Chen WC, Hsin IF, Chen PH, Hsu PI, Wang YP, Cheng JS, Lin HS, Hou MC, Lee FY. Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2019 Oct;17(11):2356-2363.e2. doi: 10.1016/j.cgh.2019.02.021. Epub 2019 Feb 14.